Venturix Possible Stroke Treatment

1. VenturixPossible Stroke Treatment Medical Technology Evaluation and Market Research MHA -- 6789 Thomas Duncan Ann Beimdiek Kinsella Shelley Oberlin

2. Agenda • Introduction to Venturix • Disease Overview • Scope of market in U.S., international, and Venturix • Market Opportunity • Current treatments/Competitors • Technology Overview • Effectiveness summary • Regulatory barriers • Conclusions • Questions

3. Venturix • Start-up company, no products on the market (founders in California and Minneapolis) • Developing an endovascular micro-catheter to remove intravascular blockages (blood clots) • Targeting three applications: • Neurothrombectomy • Chronic Total Occlusions – coronary/heart • Peripheral Vascular Disease

4. Class Project • For purposes of the class project, we have focused on evaluating the device for neural applications – specifically treatment for ischemic strokes (explained below) • Some facts about strokes . . .

5. Disease Overview • What is a stroke? • It is a type of cardiovascular disease that affects the arteries leading to and within the brain • Stroke occurs when a blood vessel to the brain is either blocked by a clot or bursts • Result is that part of the brain can’t get the blood (and oxygen) it needs **Source American Stroke Association

6. Disease Overview (cont.) • Three types of strokes • Ischemic • hemorrhagic • transient ischemic attacks (TIAs) • Ischemic – when a blood clot blocks an artery (most common type of stroke, about 83 percent) • Hemorrhagic – a weakened vessel ruptures and bleeds into the brain • TIA – minor or warning strokes (conditions of an ischemic stroke are present, with warning signs, but the blood clot occurs for a short time) **Source American Stroke Association

7. Scope of Market

8. Scope of the problem in the U.S. • Strokes are the third leading cause of death in the United States (behind heart disease and all cancers) • 700,000 strokes occur annually and approximately 300,000 people will die from strokes this year • Number of stroke victims expected to double in the next 20 years • Only 20 percent of strokes are caught in time for treatment • Leading cause of serious, long-term disability (half of survivors suffer long-term disabilities) • In 1999, more than 1.1 million American adults reported difficulty with functional limitations, activities of daily living, etc., resulting from stroke  **Source American Stroke Association, USA Today, Science Clearing the Way for Shift in Fighting Stroke, April 27, 2004)

9. Disability from a stroke (U.S.) • Among ischemic stroke survivors who were at least 65 years old, these disabilities were observed at six months post-stroke: • 50 percent had some one-sided paralysis    • 30 percent were unable to walk without some assistance • 26 percent were dependent in activities of daily living (grooming, eating, bathing, etc)     • 19 percent had aphasia (trouble speaking or understanding the speech of others) • 35 percent had depressive symptoms • 26 percent were institutionalized in a nursing home **Source American Stroke Association (National Heart, Lung, and Blood Institute's Framingham Heart Study)

10. Scope of the problem worldwide • As in the U.S., stroke is the third leading cause of death worldwide, and the leading cause of adult disability • The World Health Organization estimates that in 2001 high blood pressure contributed to more than half of the world’s 20.5 million strokes (5.5 million fatal) • 650,000 strokes fatalities each year in Europe alone • One out of every six stroke victims will suffer a second stroke within five years **Sources: World Health Report 2002, International Cardiovascular Disease Statistics (AHA) and DGNews

11. Venturix • Potential Venturix device would be used to treat ischemic strokes • 2-8 hr time window • Treatment in hospital setting • Revenues – GPOs or Hospitals • Focus on U.S. market • 700,000 strokes, 88% Ischemic, 20% caught in time • 100% market share = 123,200 potential patient population • 5-15% market share = 6,160 – 18,480 treatable patients

12. Market Opportunity • Current Treatments • Competitors

13. Current Stroke Treatments/Competitors • Preventing clots (increasing success would decrease demand for stroke treatment) • Carotid endarterectomy (surgery where blockage is surgically removed from the carotid artery) • Carotid angioplasty and stenting, less invasive than surgery (clears and props open arteries) • Very new, advisory committee recommended this week that the FDA approve the Precise stent for patients who were poor surgical candidates • Not clear either procedure prevents a stroke ** Source USA Today, Science Clearing the Way for Shift in Fighting Stroke, April 27, 2004)

14. Current Stroke Treatments/Competitors • Preventing clots (cont.) • Antiplatelet agents such as aspirin and anticoagulants such as warfarin interfere with the blood’s ability to clot and can help to prevent stroke **Source American Stroke Association

15. Treatment after onset of a stroke • Currently no surgical procedure to remove clots after stroke in progress • Similarly, no catheter device approved to remove blood clots in the brain • Only approved treatment is tPA (tissue plasminogen activator) • a clot busting drug that must be administered within three hours from the onset of symptoms (only 3 to 5 percent of stroke victims reach the hospital in time to be considered for tPA)

16. tPA Treatment (cont.) • Widely divergent views on the benefits of tPA for those that do arrive in time • Use of tPA not the standard of care for Canadian Association of Emergency Physicians, American Academy of Emergency Medicine, or the American College of Emergency Physicians

17. Competitors • Indirect – stroke prevention (discussed above) • Direct • Possis – Angiojet • While safe, did not meet the effectiveness challenges to warrant phase II of clinical trials • Concentric – Merci Retriever • Works in only 50% of cases • FDA rejected device for treatment of strokes • Uncomfortable with the single arm/non-randomized clinical trials

18. Technology Overview • What the Venturix product would do? • Catheter inserted through femoral artery • Guide wire steers catheter to brain; wire removed • Working end: uses energy and suction effects to create a focused extraction force to remove blood clots • Advantages • Does not need to penetrate the clot • Pulsatile effects to break up and remove clot • Device can be same size as blood vessel wall (bigger than competitors)

19. Effectiveness Summary of Venturix Micro-catheter • Promising prototypes developed • No clinical trials • Cost effectiveness analysis • Average cost effectiveness ratio: (Cost of intervention – Cost averted by intervention) Benefits of Intervention

20. Cost effectiveness • Cost of intervention • Cost per unit*average number of treatable patients • ($2,174*12,320) = $26.8M • Hospital costs and physician costs for 2003 • $12.6B + $2.5B • Total Cost of Intervention • $26.8M + $12,600M + $2,500M = $15.1B **Source: American Stroke Association and Venturix

21. Cost Effectiveness Costs averted by Intervention

22. Cost Effectiveness • Benefits of Intervention • Assumptions • Assume QALY of a stroke victim is 0 – 0.5 (rationale, death from stroke, high disability rate for survivors) • Assume QALY after onset of stroke and treatment with Venturix device (for those that reach hospital in time) of 0.7 – 0.8 (clot removed, disability prevented) • Ratio Analysis • Change in net costs = -36.1M • tPA – cost savings (CEA registry)

23. Regulatory Barriers • Most likely a Class III device requiring pre-market approval • The pre-market approval (PMA) process is more involved and includes the submission of clinical data to support claims made for the device. • Approval is based on a determination by the FDA that the PMA contains sufficient valid scientific evidence to assure that the device is safe and effective for its intended use(s). • Requires clinical information such as (study protocols, safety and effectiveness data, adverse reactions and complications, device failures and replacements, patient information, patient complaints, results of statistical analyses, and any other information from the clinical investigations). • Before approving or denying a PMA, the appropriate FDA advisory committee may review the PMA at a public meeting and provide FDA with the committee's recommendation on whether FDA should approve the submission. **Source FDA website

24. Conclusions • Market need and market opportunity for stoke treatment • Venturix has promising prototypes but will need to make the device smaller and demonstrate that it is safe and effective • Competitors ahead of them in terms of development and FDA approval • An in depth CE analysis is going to be a challenge but is necessary and will be beneficial

25. Questions?